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Multiplex-GAM: genome-wide identification of chromatin contacts yields insights overlooked by Hi-C

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Item Type:Article
Title:Multiplex-GAM: genome-wide identification of chromatin contacts yields insights overlooked by Hi-C
Creators: Beagrie, R.A. ORCID logoORCID: https://orcid.org/0000-0003-1076-5595, Thieme, C.J. ORCID logoORCID: https://orcid.org/0000-0002-1566-0971, Annunziatella, C., Baugher, C., Zhang, Y., Schueler, M., Kukalev, A. ORCID logoORCID: https://orcid.org/0000-0001-5847-3773, Kempfer, R. ORCID logoORCID: https://orcid.org/0000-0002-8588-8576, Chiariello, A.M. ORCID logoORCID: https://orcid.org/0000-0002-6112-0167, Bianco, S. ORCID logoORCID: https://orcid.org/0000-0001-5819-060X, Li, Y. ORCID logoORCID: https://orcid.org/0000-0001-5791-096X, Davis, T., Scialdone, A. ORCID logoORCID: https://orcid.org/0000-0002-4956-2843, Welch, L.R. ORCID logoORCID: https://orcid.org/0000-0001-6419-9416, Nicodemi, M. ORCID logoORCID: https://orcid.org/0000-0002-8416-6416 and Pombo, A. ORCID logoORCID: https://orcid.org/0000-0002-7493-6288
Abstract:Technology for measuring 3D genome topology is increasingly important for studying gene regulation, for genome assembly and for mapping of genome rearrangements. Hi-C and other ligation-based methods have become routine but have specific biases. Here, we develop multiplex-GAM, a faster and more affordable version of genome architecture mapping (GAM), a ligation-free technique that maps chromatin contacts genome-wide. We perform a detailed comparison of multiplex-GAM and Hi-C using mouse embryonic stem cells. When examining the strongest contacts detected by either method, we find that only one-third of these are shared. The strongest contacts specifically found in GAM often involve ‘active’ regions, including many transcribed genes and super-enhancers, whereas in Hi-C they more often contain ‘inactive’ regions. Our work shows that active genomic regions are involved in extensive complex contacts that are currently underestimated in ligation-based approaches, and highlights the need for orthogonal advances in genome-wide contact mapping technologies.
Keywords:Chromatin Analysis, Chromatin Structure, DNA Sequencing, Epigenomics, Genome Informatics, Animals, Mice
Source:Nature Methods
ISSN:1548-7091
Publisher:Nature Publishing Group
Volume:20
Number:7
Page Range:1037-1047
Date:July 2023
Official Publication:https://doi.org/10.1038/s41592-023-01903-1
PubMed:View item in PubMed

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